CA2225325A1 - Hemiasterlin analogs - Google Patents

Hemiasterlin analogs Download PDF

Info

Publication number: CA2225325A1
Authority: CA; Canada
Prior art keywords: compound; group; formula; arr; butyl
Prior art date: 1997-12-19
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002225325A

Other languages

English (en)

French (fr)

Inventor

Michel Roberge

Edward Piers

James Nieman

Raymond Andersen

John Coleman

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

University of British Columbia

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-12-19

Filing date

1997-12-19

Publication date

1999-06-19

1997-12-19 Application filed by University of British Columbia filed Critical University of British Columbia

1997-12-19 Priority to CA002225325A priority Critical patent/CA2225325A1/en

1998-12-13 Priority to US09/581,511 priority patent/US7579323B1/en

1998-12-18 Priority to IL13665498A priority patent/IL136654A0/xx

1998-12-18 Priority to EP98962157A priority patent/EP1040119B1/en

1998-12-18 Priority to NZ505086A priority patent/NZ505086A/en

1998-12-18 Priority to DK98962157T priority patent/DK1040119T3/da

1998-12-18 Priority to AT98962157T priority patent/ATE419268T1/de

1998-12-18 Priority to PCT/CA1998/001184 priority patent/WO1999032509A2/en

1998-12-18 Priority to JP2000525446A priority patent/JP4417551B2/ja

1998-12-18 Priority to ES98962157T priority patent/ES2320499T3/es

1998-12-18 Priority to BR9813817-0A priority patent/BR9813817A/pt

1998-12-18 Priority to HU0105460A priority patent/HUP0105460A3/hu

1998-12-18 Priority to KR1020007006814A priority patent/KR100937756B1/ko

1998-12-18 Priority to DE69840415T priority patent/DE69840415D1/de

1998-12-18 Priority to CNB988124343A priority patent/CN100422208C/zh

1998-12-18 Priority to CA2312826A priority patent/CA2312826C/en

1998-12-18 Priority to AU17459/99A priority patent/AU762691C/en

1999-06-19 Publication of CA2225325A1 publication Critical patent/CA2225325A1/en

2001-07-31 Priority to HK01105313.8A priority patent/HK1034523A1/xx

2009-06-25 Priority to US12/491,839 priority patent/US20090264487A1/en

Status Abandoned legal-status Critical Current

Links

KQODQNJLJQHFQV-MKWZWQCGSA-N (e,4s)-4-[[(2s)-3,3-dimethyl-2-[[(2s)-3-methyl-2-(methylamino)-3-(1-methylindol-3-yl)butanoyl]amino]butanoyl]-methylamino]-2,5-dimethylhex-2-enoic acid Chemical class C1=CC=C2C(C(C)(C)[C@@H](C(=O)N[C@H](C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-MKWZWQCGSA-N 0.000 title abstract description 14
238000000034 method Methods 0.000 claims abstract description 36
150000001875 compounds Chemical class 0.000 claims description 89
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 37
-1 anthracyl Chemical group 0.000 claims description 14
229920006395 saturated elastomer Polymers 0.000 claims description 14
108010016626 Dipeptides Proteins 0.000 claims description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
150000001413 amino acids Chemical class 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 8
238000005859 coupling reaction Methods 0.000 claims description 8
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 8
230000008878 coupling Effects 0.000 claims description 7
238000010168 coupling process Methods 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
150000003839 salts Chemical class 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 6
125000004432 carbon atom Chemical group C* 0.000 claims description 6
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000006239 protecting group Chemical group 0.000 claims description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000000168 pyrrolyl group Chemical group 0.000 claims description 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
229910006069 SO3H Inorganic materials 0.000 claims description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 2
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000006841 cyclic skeleton Chemical group 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000002883 imidazolyl group Chemical group 0.000 claims description 2
125000005956 isoquinolyl group Chemical group 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
125000005561 phenanthryl group Chemical group 0.000 claims description 2
125000004076 pyridyl group Chemical group 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000001544 thienyl group Chemical group 0.000 claims description 2
125000004417 unsaturated alkyl group Chemical group 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 1
KQODQNJLJQHFQV-UHFFFAOYSA-N (-)-hemiasterlin Natural products C1=CC=C2C(C(C)(C)C(C(=O)NC(C(=O)N(C)C(C=C(C)C(O)=O)C(C)C)C(C)(C)C)NC)=CN(C)C2=C1 KQODQNJLJQHFQV-UHFFFAOYSA-N 0.000 abstract description 12
108010057806 hemiasterlin Proteins 0.000 abstract description 12
229930187626 hemiasterlin Natural products 0.000 abstract description 12
230000015572 biosynthetic process Effects 0.000 abstract description 6
238000003786 synthesis reaction Methods 0.000 abstract description 6
230000001472 cytotoxic effect Effects 0.000 abstract description 5
231100000433 cytotoxic Toxicity 0.000 abstract description 4
239000003080 antimitotic agent Substances 0.000 abstract description 2
239000002254 cytotoxic agent Substances 0.000 abstract description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 89
239000000203 mixture Substances 0.000 description 28
239000000243 solution Substances 0.000 description 28
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
210000004027 cell Anatomy 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
101150041968 CDC13 gene Proteins 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
238000005481 NMR spectroscopy Methods 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
230000003287 optical effect Effects 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000012044 organic layer Substances 0.000 description 8
238000000746 purification Methods 0.000 description 8
238000003756 stirring Methods 0.000 description 8
229940024606 amino acid Drugs 0.000 description 7
230000002927 anti-mitotic effect Effects 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
238000001819 mass spectrum Methods 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
239000010410 layer Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
108010072471 HTI-286 Proteins 0.000 description 5
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
239000000284 extract Substances 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
239000012043 crude product Substances 0.000 description 4
KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 4
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
239000000725 suspension Substances 0.000 description 4
WZZUQWBUVSVLRT-SECBINFHSA-N tert-butyl n-methyl-n-[(2s)-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound CC(C)[C@@H](C=O)N(C)C(=O)OC(C)(C)C WZZUQWBUVSVLRT-SECBINFHSA-N 0.000 description 4
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 3
JTZZMXVIHNHASS-UHFFFAOYSA-N 3-methyl-3-phenylbutanoic acid Chemical compound OC(=O)CC(C)(C)C1=CC=CC=C1 JTZZMXVIHNHASS-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
229910052786 argon Inorganic materials 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
150000001540 azides Chemical class 0.000 description 3
230000037396 body weight Effects 0.000 description 3
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150000002148 esters Chemical class 0.000 description 3
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125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 3
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YIZNGYBBIZTTAF-CYBMUJFWSA-N methyl (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylbutanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)C(C)(C)C1=CC=CC=C1 YIZNGYBBIZTTAF-CYBMUJFWSA-N 0.000 description 3
230000011278 mitosis Effects 0.000 description 3
230000000394 mitotic effect Effects 0.000 description 3
239000000047 product Substances 0.000 description 3
239000000523 sample Substances 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000007787 solid Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
210000004881 tumor cell Anatomy 0.000 description 3
XPUAXAVJMJDPDH-QMMMGPOBSA-N (2s)-3-methyl-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)N(C)C(=O)OC(C)(C)C XPUAXAVJMJDPDH-QMMMGPOBSA-N 0.000 description 2
AEMWUHCKKDPRSK-UHFFFAOYSA-N (ne)-n-diazo-2,4,6-tri(propan-2-yl)benzenesulfonamide Chemical compound CC(C)C1=CC(C(C)C)=C(S(=O)(=O)N=[N+]=[N-])C(C(C)C)=C1 AEMWUHCKKDPRSK-UHFFFAOYSA-N 0.000 description 2
238000005160 1H NMR spectroscopy Methods 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
YYPNJNDODFVZLE-UHFFFAOYSA-N 3-methylbut-2-enoic acid Chemical compound CC(C)=CC(O)=O YYPNJNDODFVZLE-UHFFFAOYSA-N 0.000 description 2
YBUPWRYTXGAWJX-UHFFFAOYSA-N 4-propan-2-yl-1,3-oxazolidin-2-one Chemical compound CC(C)C1COC(=O)N1 YBUPWRYTXGAWJX-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
238000002965 ELISA Methods 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
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MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
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JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
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DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
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238000010561 standard procedure Methods 0.000 description 2
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UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
XQMVBICWFFHDNN-UHFFFAOYSA-N 5-amino-4-chloro-2-phenylpyridazin-3-one;(2-ethoxy-3,3-dimethyl-2h-1-benzofuran-5-yl) methanesulfonate Chemical compound O=C1C(Cl)=C(N)C=NN1C1=CC=CC=C1.C1=C(OS(C)(=O)=O)C=C2C(C)(C)C(OCC)OC2=C1 XQMVBICWFFHDNN-UHFFFAOYSA-N 0.000 description 1
239000005995 Aluminium silicate Substances 0.000 description 1
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241000283707 Capra Species 0.000 description 1
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VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
239000004375 Dextrin Substances 0.000 description 1
229920001353 Dextrin Polymers 0.000 description 1
240000006497 Dianthus caryophyllus Species 0.000 description 1
235000009355 Dianthus caryophyllus Nutrition 0.000 description 1
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
239000004150 EU approved colour Substances 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000001856 Ethyl cellulose Substances 0.000 description 1
ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
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ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
229930182816 L-glutamine Natural products 0.000 description 1
239000004166 Lanolin Substances 0.000 description 1
WGCKDDHUFPQSMZ-ZPFDUUQYSA-N Lys-Asp-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](N)CCCCN WGCKDDHUFPQSMZ-ZPFDUUQYSA-N 0.000 description 1
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IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Molecular Biology (AREA)
Genetics & Genomics (AREA)
Biophysics (AREA)
Biochemistry (AREA)
Crystallography & Structural Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Peptides Or Proteins (AREA)
Junction Field-Effect Transistors (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Amplifiers (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pyrrole Compounds (AREA)

CA002225325A 1997-12-19 1997-12-19 Hemiasterlin analogs Abandoned CA2225325A1 (en)

Priority Applications (19)

Application Number	Priority Date	Filing Date	Title
CA002225325A CA2225325A1 (en)	1997-12-19	1997-12-19	Hemiasterlin analogs
US09/581,511 US7579323B1 (en)	1997-12-19	1998-12-13	Hemiasterlin analogs
ES98962157T ES2320499T3 (es)	1997-12-19	1998-12-18	Analogos de hemiasterlina.
HU0105460A HUP0105460A3 (en)	1997-12-19	1998-12-18	Hemiasterlin analogs and process for preparation thereof
NZ505086A NZ505086A (en)	1997-12-19	1998-12-18	Dipeptide and tripeptide hemiasterlin analogs
DK98962157T DK1040119T3 (da)	1997-12-19	1998-12-18	Hemiasterlinanaloger
AT98962157T ATE419268T1 (de)	1997-12-19	1998-12-18	Haemasterlin analoge
PCT/CA1998/001184 WO1999032509A2 (en)	1997-12-19	1998-12-18	Hemiasterlin analogs
JP2000525446A JP4417551B2 (ja)	1997-12-19	1998-12-18	ヘミアスターリン類似体
IL13665498A IL136654A0 (en)	1997-12-19	1998-12-18	Hemiasterlin analogs
BR9813817-0A BR9813817A (pt)	1997-12-19	1998-12-18	Análogos de hemiasterlina
EP98962157A EP1040119B1 (en)	1997-12-19	1998-12-18	Hemiasterlin analogs
KR1020007006814A KR100937756B1 (ko)	1997-12-19	1998-12-18	헤미아스테르린 유사체
DE69840415T DE69840415D1 (de)	1997-12-19	1998-12-18	Haemasterlin analoge
CNB988124343A CN100422208C (zh)	1997-12-19	1998-12-18	半海盘灵类似物
CA2312826A CA2312826C (en)	1997-12-19	1998-12-18	Hemiasterlin analogs
AU17459/99A AU762691C (en)	1997-12-19	1998-12-18	Hemiasterlin analogs
HK01105313.8A HK1034523A1 (en)	1997-12-19	2001-07-31	Hemiasterlin analogs
US12/491,839 US20090264487A1 (en)	1997-12-19	2009-06-25	Hemiasterlin analogs

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA002225325A CA2225325A1 (en)	1997-12-19	1997-12-19	Hemiasterlin analogs

Publications (1)

Publication Number	Publication Date
CA2225325A1 true CA2225325A1 (en)	1999-06-19

Family

ID=4161925

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA002225325A Abandoned CA2225325A1 (en)	1997-12-19	1997-12-19	Hemiasterlin analogs
CA2312826A Expired - Fee Related CA2312826C (en)	1997-12-19	1998-12-18	Hemiasterlin analogs

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA2312826A Expired - Fee Related CA2312826C (en)	1997-12-19	1998-12-18	Hemiasterlin analogs

Country Status (17)

Country	Link
US (2)	US7579323B1 (ja)
EP (1)	EP1040119B1 (ja)
JP (1)	JP4417551B2 (ja)
KR (1)	KR100937756B1 (ja)
CN (1)	CN100422208C (ja)
AT (1)	ATE419268T1 (ja)
AU (1)	AU762691C (ja)
BR (1)	BR9813817A (ja)
CA (2)	CA2225325A1 (ja)
DE (1)	DE69840415D1 (ja)
DK (1)	DK1040119T3 (ja)
ES (1)	ES2320499T3 (ja)
HK (1)	HK1034523A1 (ja)
HU (1)	HUP0105460A3 (ja)
IL (1)	IL136654A0 (ja)
NZ (1)	NZ505086A (ja)
WO (1)	WO1999032509A2 (ja)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2003072754A2 (en) *	2002-02-27	2003-09-04	The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services	Conjugates of ligand, linker and cytotoxic agent and related compositions and methods of use
NZ555951A (en) *	2002-03-22	2009-01-31	Eisai Co Ltd	Hemiasterlin derivatives and uses thereof
US7064211B2 (en)	2002-03-22	2006-06-20	Eisai Co., Ltd.	Hemiasterlin derivatives and uses thereof
EP1539682A2 (en) *	2002-09-20	2005-06-15	Wyeth Holdings Corporation	Process for the synthesis of intermediates useful for the synthesis of tubulin inhibitors
US20040121965A1 (en) *	2002-09-20	2004-06-24	Wyeth Holdings Corporation	Method of treating resistant tumors
WO2004047615A2 (en) *	2002-11-21	2004-06-10	Wyeth	Hemiasterlin affinity probes and their uses
US7390910B2 (en) *	2003-08-08	2008-06-24	Wyeth	Compounds for treating tumors
GB201001070D0 (en)	2010-01-22	2010-03-10	St George's Hospital Medical School	Theraputic compounds and their use
EP2968440B1 (en)	2013-03-15	2019-06-05	Zymeworks Inc.	Cytotoxic and anti-mitotic compounds, and methods of using the same
MX2016008448A (es)	2013-12-27	2017-01-09	Zymeworks Inc	Conjugados de var2csa-farmaco.
PL3086815T3 (pl)	2013-12-27	2022-06-13	Zymeworks Inc.	Układy łącznikowe dla koniugatów leków zawierające ugrupowanie sulfonamidowe
BR112017005126B1 (pt)	2014-09-17	2023-10-24	Zymeworks Inc	Composto citotóxico e antimitótico, composições, composição farmacêutica, uso do referido composto e uso das referidas composições
CN114716506A (zh)	2015-01-30	2022-07-08	苏特罗生物制药公司	用于偶联和治疗的哈米特林（hemiasterlin）衍生物
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1997
- 1997-12-19 CA CA002225325A patent/CA2225325A1/en not_active Abandoned
1998
- 1998-12-13 US US09/581,511 patent/US7579323B1/en not_active Expired - Fee Related
- 1998-12-18 BR BR9813817-0A patent/BR9813817A/pt not_active Application Discontinuation
- 1998-12-18 HU HU0105460A patent/HUP0105460A3/hu unknown
- 1998-12-18 DE DE69840415T patent/DE69840415D1/de not_active Expired - Lifetime
- 1998-12-18 EP EP98962157A patent/EP1040119B1/en not_active Expired - Lifetime
- 1998-12-18 DK DK98962157T patent/DK1040119T3/da active
- 1998-12-18 IL IL13665498A patent/IL136654A0/xx unknown
- 1998-12-18 JP JP2000525446A patent/JP4417551B2/ja not_active Expired - Fee Related
- 1998-12-18 CA CA2312826A patent/CA2312826C/en not_active Expired - Fee Related
- 1998-12-18 AU AU17459/99A patent/AU762691C/en not_active Ceased
- 1998-12-18 WO PCT/CA1998/001184 patent/WO1999032509A2/en active IP Right Grant
- 1998-12-18 ES ES98962157T patent/ES2320499T3/es not_active Expired - Lifetime
- 1998-12-18 NZ NZ505086A patent/NZ505086A/en unknown
- 1998-12-18 KR KR1020007006814A patent/KR100937756B1/ko not_active IP Right Cessation
- 1998-12-18 CN CNB988124343A patent/CN100422208C/zh not_active Expired - Fee Related
- 1998-12-18 AT AT98962157T patent/ATE419268T1/de not_active IP Right Cessation
2001
- 2001-07-31 HK HK01105313.8A patent/HK1034523A1/xx not_active IP Right Cessation
2009
- 2009-06-25 US US12/491,839 patent/US20090264487A1/en not_active Abandoned

Also Published As

Publication number	Publication date
IL136654A0 (en)	2001-06-14
EP1040119A2 (en)	2000-10-04
HUP0105460A2 (en)	2002-06-29
CA2312826C (en)	2013-06-11
HK1034523A1 (en)	2001-10-26
DE69840415D1 (de)	2009-02-12
KR20010024783A (ko)	2001-03-26
DK1040119T3 (da)	2009-04-14
US7579323B1 (en)	2009-08-25
US20090264487A1 (en)	2009-10-22
CA2312826A1 (en)	1999-07-01
NZ505086A (en)	2003-05-30
ATE419268T1 (de)	2009-01-15
AU762691C (en)	2004-07-08
CN100422208C (zh)	2008-10-01
HUP0105460A3 (en)	2002-08-28
JP4417551B2 (ja)	2010-02-17
WO1999032509A3 (en)	1999-10-07
BR9813817A (pt)	2000-10-10
ES2320499T3 (es)	2009-05-22
AU1745999A (en)	1999-07-12
AU762691B2 (en)	2003-07-03
EP1040119B1 (en)	2008-12-31
WO1999032509A2 (en)	1999-07-01
KR100937756B1 (ko)	2010-01-20
JP2001526294A (ja)	2001-12-18
CN1282336A (zh)	2001-01-31

Publication	Publication Date	Title
US20090264487A1 (en)	2009-10-22	Hemiasterlin analogs
US6153590A (en)	2000-11-28	Biologically active peptides and compositions, their use
US5714471A (en)	1998-02-03	Peptide and peptide analog protease inhibitors
AU714147B2 (en)	1999-12-23	Inhibitors of farnesyl protein transferase
US5312831A (en)	1994-05-17	Urethanes and ureas that induce cytokine production
EP0750609A4 (en)	1997-09-24	ISOPRENYLE TRANSFERASE INHIBITORS
CA2022692A1 (en)	1991-02-06	Renin inhibitors
HRP960008A2 (en)	1998-04-30	Proline derivatives
TW200524578A (en)	2005-08-01	Protease inhibitors
Dahiya et al.	2007	First total synthesis and biological evaluation of halolitoralin A
US4487763A (en)	1984-12-11	Peptide, process for preparation thereof and use thereof
US20050107288A1 (en)	2005-05-19	Antibacterial macrocycles
AU2002312656B2 (en)	2008-06-12	Peptoid compounds
MXPA00005677A (en)	2001-07-03	Hemiasterlin analogs
US4714757A (en)	1987-12-22	Aminopeptidase inhibitors

Legal Events

Date	Code	Title	Description
2000-03-22	FZDE	Discontinued